PubMed Health⌕ Search

Biomedical subjects

C Goutte

Publications and source records attributed to C Goutte.

12 recordsLinked to original sources

APH-2/nicastrin functions in LIN-12/Notch signaling in the Caenorhabditis elegans somatic gonad.

Nicastrin is a recently identified member of high-molecular weight complexes containing presenilin. The Caenorhabditis elegans homolog of nicastrin, aph-2, was shown to be required for GLP-1/Notch signaling in the early embryo. In addition to the maternal-effect embryonic lethal phenotype, aph-2 mutant animals also display an egg-laying defect. We show that this latter defect is related to the SEL-12/presenilin egg-laying defect. We also show that aph-2 and sel-12 genetically interact and cooperate to regulate LIN-12/Notch signaling in the development of the somatic gonad. In addition, aph-2 and lin-12/Notch genetically interact. We illustrate a new role for aph-2 in facilitating lin-12 signaling in the somatic gonad, thus providing evidence that APH-2 is involved in both GLP-1/Notch- and LIN-12/Notch-mediated signaling events. Finally, we demonstrate that nicastrin can partially substitute for aph-2, suggesting a conservation of function between these proteins.

Amyloid Precursor Protein Secretases↗

Feature-space clustering for fMRI meta-analysis.

Clustering functional magnetic resonance imaging (fMRI) time series has emerged in recent years as a possible alternative to parametric modeling approaches. Most of the work so far has been concerned with clustering raw time series. In this contribution we investigate the applicability of a clustering method applied to features extracted from the data. This approach is extremely versatile and encompasses previously published results [Goutte et al., 1999] as special cases. A typical application is in data reduction: as the increase in temporal resolution of fMRI experiments routinely yields fMRI sequences containing several hundreds of images, it is sometimes necessary to invoke feature extraction to reduce the dimensionality of the data space. A second interesting application is in the meta-analysis of fMRI experiment, where features are obtained from a possibly large number of single-voxel analyses. In particular this allows the checking of the differences and agreements between different methods of analysis. Both approaches are illustrated on a fMRI data set involving visual stimulation, and we show that the feature space clustering approach yields nontrivial results and, in particular, shows interesting differences between individual voxel analysis performed with traditional methods.

Algorithms↗

Modeling the haemodynamic response in fMRI using smooth FIR filters.

Modeling the haemodynamic response in functional magnetic resonance (fMRI) experiments is an important aspect of the analysis of functional neuroimages. This has been done in the past using parametric response function, from a limited family. In this contribution, we adopt a semi-parametric approach based on finite impulse response (FIR) filters. In order to cope with the increase in the number of degrees of freedom, we introduce a Gaussian process prior on the filter parameters. We show how to carry on the analysis by incorporating prior knowledge on the filters, optimizing hyper-parameters using the evidence framework, or sampling using a Markov Chain Monte Carlo (MCMC) approach. We present a comparison of our model with standard haemodynamic response kernels on simulated data, and perform a full analysis of data acquired during an experiment involving visual stimulation.

Hemodynamics↗

aph-2 encodes a novel extracellular protein required for GLP-1-mediated signaling.

In animal development, numerous cell-cell interactions are mediated by the GLP-1/LIN-12/NOTCH family of transmembrane receptors. These proteins function in a signaling pathway that appears to be conserved from nematodes to humans. We show here that the aph-2 gene is a new component of the GLP-1 signaling pathway in the early Caenorhabditis elegans embryo, and that proteins with sequence similarity to the APH-2 protein are found in Drosophila and vertebrates. During the GLP-1-mediated cell interactions in the C. elegans embryo, APH-2 is associated with the cell surfaces of both the signaling, and the responding, blastomeres. Analysis of chimeric embryos that are composed of aph-2(+) and aph-2(-) blastomeres suggests that aph-2(+) function may be provided by either the signaling or responding blastomere.

Amino Acid Sequence↗

On clustering fMRI time series.

Analysis of fMRI time series is often performed by extracting one or more parameters for the individual voxels. Methods based, e.g., on various statistical tests are then used to yield parameters corresponding to probability of activation or activation strength. However, these methods do not indicate whether sets of voxels are activated in a similar way or in different ways. Typically, delays between two activated signals are not identified. In this article, we use clustering methods to detect similarities in activation between voxels. We employ a novel metric that measures the similarity between the activation stimulus and the fMRI signal. We present two different clustering algorithms and use them to identify regions of similar activations in an fMRI experiment involving a visual stimulus.

Algorithms↗

Recognition of a DNA operator by a dimer composed of two different homeodomain proteins.

The yeast homeodomain proteins a1 and alpha 2 interact to form a heterodimer that binds DNA with high specificity. The DNA recognition element consists of two similar half sites, arranged with dyad symmetry and separated by a fixed number of base pairs. We demonstrate that in the a1 alpha 2-DNA complex, one of these half-sites is bound by a1 while the other is bound by alpha 2. These assignments allow a comparison of the chemical and nuclease protection patterns produced by both proteins when bound together to the hsg operator. Contrary to simple expectations, we propose that the a1 and alpha 2 homeodomains are arranged on the DNA in tandem, despite the fact that the recognition sequence is dyad symmetric.

Base Sequence↗

Yeast a1 and alpha 2 homeodomain proteins form a DNA-binding activity with properties distinct from those of either protein.

The yeast a1 and alpha 2 proteins are examples of homeodomain proteins that display cell-type-specific expression. They are co-expressed in only one type of cell, the a/alpha cell, where they repress the expression of a group of target genes. Using purified proteins, we demonstrate that a1 and alpha 2 form a highly specific DNA-binding activity, which recognizes an operator found upstream of each target gene. These proteins interact with DNA to form a ternary complex in which both a1 and alpha 2 contact the DNA through their respective homeodomains. An alpha 2 homodimer can recognize the same operator as the a1/alpha 2 heterodimer, but the affinity and specificity of the alpha 2 homodimer for DNA are much weaker than those of the a1/alpha 2 heterodimer. This difference results in part from the fact that the heterodimer is formed using a set of protein-protein contacts that is distinct from those that form the alpha 2/alpha 2 homodimer. Although a1 contacts DNA in the presence of alpha 2, it does not on its own bind DNA specifically, even at very high concentrations. These results suggest that the dimerization of heterologous partners can produce a DNA-binding activity that is not a simple hybrid of the known properties of each constituent.

Base Sequence↗

The yeast cell-type-specific repressor alpha 2 acts cooperatively with a non-cell-type-specific protein.

The yeast alpha 2 protein is a cell-type-specific transcriptional repressor. It acts by binding to an operator located upstream of each of its target genes. In this paper, we describe a protein (GRM) that is present in all cell types and binds cooperatively with alpha 2 resulting in an unusual arrangement of the two proteins at the operator. A dimer of alpha 2 occupies the two ends of the operator and straddles the GRM protein, which binds to the center of the operator. Using mutant operators, we show that the recognition sequences for both GRM and alpha 2 are required for repression of a test promoter in vivo. Finally, we deduce that the GRM/alpha 2 cooperativity is mediated through a protein-protein interaction between GRM and the N-terminal domain of alpha 2. This conclusion follows from the observation that the isolated C-terminal domain of alpha 2 can co-occupy the operator with GRM but does not bind cooperatively with GRM.

Base Sequence↗

a1 protein alters the DNA binding specificity of alpha 2 repressor.

The alpha 2 protein of S. cerevisiae, the product of the MAT alpha 2 gene, represses a set of cell-type-specific genes (the a-specific genes) by binding to an operator sequence upstream of each gene. We demonstrate that a second yeast regulatory protein, a1, the product of the MATa1 gene, can alter the binding specificity of alpha 2 so that it no longer recognizes the a-specific gene operator, but instead acquires the ability to recognize a different operator sequence found upstream of haploid-specific genes. Thus, under the influence of a1, alpha 2 can repress haploid-specific genes. An alpha cell expresses alpha 2 but not a1, so that alpha 2 turns off only the a-specific genes. An a/alpha cell makes both a1 and alpha 2, in a ratio that ensures that alpha 2 is distributed between two distinct binding modes: the alpha 2 binding mode and the a1-alpha 2 binding mode. Thus in an a/alpha cell, alpha 2 represses two distinct classes of genes.

Chromosome Deletion↗